Paliperidone is an atypical antipsychotic drug, also known as second generation antipsychotic drug and is described in U.S. Pat. No. 4,804,663. It is practically insoluble in water, and sparingly soluble in 0.1 N HCl and methylene chloride.
Janssen-Ortho Inc markets extended release formulations of paliperidone, under the trade name of Invega® and are available in strengths of 1.5 mg, 3 mg, 6 mg and 9 mg. The said formulation employs an osmotic drug-release technology (OROS) to provide a “gradual ascending” drug delivery to minimize fluctuation in peak to trough concentration and permits 24 hour dosing interval.
WO2004010981 and EP1539115 disclose extended release formulations and methods for providing ascending rate of release of paliperidone utilizing a capsule-shaped tablet for once a day dosing. The dosage form utilizes a semipermiable membrane surrounding a three layer core: i) the first layer contains drug and an osmotic agent; ii) the middle layer contains higher amount of drug and without osmotic agent and iii) the third layer is a push layer containing osmotic agent. The capsule shaped tablet contains at least one orifice, which is drilled through the membrane on the first drug layer.
U.S. patent application 2006034927 discloses a paliperidone dosage form for sustained release of paliperidone comprising:    a delay layer comprising (i) a polymeric matrix, and (ii) microencapsulated drug, wherein the delay layer is substantially free of non-microencapsulated drug;    a second layer comprising (i) a polymeric matrix, and (ii) non-microencapsulated drug matrix; wherein the second layer is located adjacent to the delay layer.
U.S. patent application 20040092534 and U.S. patent application 20090202631 disclose a method for treating a condition responsive to paliperidone. The dosage form comprises:    (a) a capsule shaped tablet core comprising plurality of layers wherein at least one layer is a drug composition layer containing an active agent and at least one other layer comprises a suitable fluid-expandable polymer;    (b) a semipermeable membrane surrounding the capsule shaped tablet core to form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting the semipermeable membrane into the compartment; and    (c) an orifice formed through the semipermeable membrane and into the capsule shaped tablet core to permit the active agent to be released from within the compartment into the external fluid environment;    wherein the dosage form releases the active agent at a substantially ascending release rate for a prolonged period of time.
WO2009025859 relates to an extended release inlay tablet of paliperidone. The inlay tablet comprises at least an inlay core and outer layer wherein the inlay core comprises non-coated paliperidone and at least one polymer capable of swelling upon hydration and delaying the release of paliperidone from the inlay core. The inlay core optionally further comprises coated paliperidone. The outer layer partially surrounds the inlay core and comprises a pharmaceutical excipient which is substantially water insoluble.
WO2009109993 relates to extended release matrix compositions of micronized paliperidone, matrix agent and surfactant. The matrix agent is selected from insoluble release controlling agent or hydrophilic release controlling agent or fatty release controlling agent. In these compositions the surfactant and micronized paliperidone are essentially used to enhance the solubility of paliperidone. The particle size distribution of paliperidone is such that 90% particles of paliperidone are less than 30 micron, preferably less than 20 micron and more preferably less than 10 micron.
WO2010009900 relates to a solid pharmaceutical composition comprising monolithic matrix system (MMS) and/or multiparticulate matrix system (MPMS) comprising paliperidone and matrix forming agent. The matrix forming agent is more preferably present in an amount from 60-98% w/w of matrix particles that prolongs the release of paliperidone. The average particle diameter of paliperidone is in the range of 1-250 μm, preferably 5-150 μm. The composition further comprises surfactant and water penetration enhancer to improve the solubility of paliperidone.
WO2009026621 relates to particulates of paliperidone, or pharmaceutically acceptable salts thereof, having D50 particle size distribution of between about 1 micron to about 40 micron.
The compositions of the above mentioned prior art have one or more of the following essential requirements:    1. Use of surfactant and water penetration enhancer;    2. Use of excipient like osmogent;    3. Use of release controlling agent (matrix forming agent) which is preferably at least 60% by weight;    4. Additional process step of drilling an orifice through the semipermeable membrane to enable the release of drug from the system.